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Background Materials and Methods Results Conclusions α‐1 blockers and dutasteride are widely used as agents to treat benign prostatic hyperplasia (BPH); the impact of these drugs on prostatic inflammation is still unclear. Herein, we investigated the impact of α‐1 blockers and dutasteride treatment of BPH in terms of the degree of prostatic inflammation.Tissue specimens were obtained from 143 BPH patients who were administered α‐1 blockers up until their operation. Thirty‐three of the patients had also been treated with dutasteride before the procedure. The degree of prostatic inflammation was quantified histologically by the ratio of high endothelial venule (HEV)‐like vessels. We divided this retrospective cohort into α‐1 blocker monotherapy and combination therapy (α‐1 blockers + dutasteride) groups and evaluated clinical parameters of the two groups in relation to the degree of chronic prostatic inflammation. At the same time, we assessed factors exacerbating chronic prostatic inflammation.Comparison of the monotherapy and combination therapy groups showed no significant differences in the parameters of the urodynamic study or degree of chronic prostatic inflammation, whereas the IPSS total score, voiding subscore, nocturia, intermittency, weak stream, and straining were significantly lower in the combination than the monotherapy group. The duration of α‐1 blockers administration was not correlated with the ratio of HEV‐like vessels, while that of dutasteride was strongly correlated (correlation coefficient = 0.595; p < 0.001). Multiple regression analysis demonstrated that the duration of dutasteride administration was a key factor exacerbating the degree of chronic prostatic inflammation.The present study showed that despite their ameliorating effect on prostatic hyperplasia, dutasteride contributed significantly to chronic prostatic inflammation. [ABSTRACT FROM AUTHOR]

Dutasteride 0.5 mg is a dual inhibitor of 5α‐reductase type I and II and was approved in Korea in 2009 for treating androgenetic alopecia (AGA) in men. We investigated the 5‐year efficacy and safety of dutasteride 0.5 mg in Korean men with AGA using the basic and specific (BASP) classification. This retrospective analysis included 99 male AGA patients aged ≥18 years who were treated with dutasteride 0.5 mg for at least 5 years from October 2009 to December 2016 at Kyung Hee University Hospital in Gangdong. Patient photographs were scored using the BASP classification, and the Investigator Global Assessment (IGA) was performed using a seven‐point scale. Patient improvement (IGA score ≥1) and prevention of disease progression (IGA score ≥0) were 89.9% (89/99) and 93.9% (93/99), respectively. According to the BASP classification, 52.5% (52/99) of the basic type, 75% (15/20) of the specific F type, and 82.2% (60/73) of the specific V type showed clinical improvement after 5 years of treatment. Dutasteride demonstrated long‐term safety and efficacy in Korean male patients with AGA over a period of at least 5 years, with results comparable to those of other long‐term efficacy studies of finasteride 1 mg in male patients with AGA. [ABSTRACT FROM AUTHOR]

Background: Minoxidil and the 5‐alpha reductase inhibitors (5‐ARIs), specifically, dutasteride and finasteride, are usually used to treat pattern hair loss (PHL), but evidence on the relative effectiveness of these drugs is far less for women than men. Aims: We performed an age‐adjusted network meta‐analysis (NMA) to determine the comparative efficacy of monotherapy with the three agents—in any dosage and administrative route—on PHL in adult women. Methods: The peer‐reviewed literature was systematically reviewed to obtain data for our NMA. The outcome measure for our NMA was "change in total hair density." We referred to "regimen" as an "agent and its dosage;" our Bayesian NMA estimated regimens' surface under the cumulative ranking curve (SUCRA) values and pairwise relative effects. Results: Our NMA used data from 13 trials—across which the following 10 regimens were identified (in decreasing order of SUCRA): 5 mg/day finasteride for 24 weeks (SUCRA = 95.7%), 5% topical minoxidil solution twice daily for 24 weeks (SUCRA = 89.5%), 1 mg/day minoxidil for 24 weeks (SUCRA = 78.1%), 5% topical minoxidil foam 1 half capful/day for 24 weeks (SUCRA = 66.5%), 3% topical minoxidil solution 1 mL twice daily for 24 weeks (SUCRA = 45.1%), 2% topical minoxidil solution 1 mL twice daily for 24 weeks (SUCRA = 44.6%), 5% topical minoxidil solution 1 mL/day for 24 weeks (SUCRA = 41.7%), 0.25 mg/day minoxidil for 24 weeks (SUCRA = 35.5%), 1.25 mg/day finasteride for 24 weeks (SUCRA = 24.8%) and 1 mg/day finasteride for 24 weeks (SUCRA = 4.3%). Conclusion: Our findings can improve clinical guidelines and help dermatologists manage female PHL more optimally with the available options. [ABSTRACT FROM AUTHOR]

The development of a novel therapy to overcome primary and acquired resistance to abiraterone is an unmet need. This study aimed to evaluate the efficacy and safety of adding 5α‐reductase inhibitor dutasteride to abiraterone, explore proof of concept, and identify candidates suitable for combination therapy. This phase II, single‐arm, and open‐label study enrolled second‐generation antiandrogen‐ and chemotherapy‐naïve patients with castration‐resistant prostate cancer. Patients received abiraterone and prednisolone for 4 weeks, followed by adding dutasteride. The primary end point was a 50% prostate‐specific antigen response rate. Serum concentrations of abiraterone and its metabolites as well as HSD3B1 and SRD5A2 genotypes were measured. The association between drug metabolism and genotypes and their impact on the efficacy of combination therapy were assessed. Among 21 patients, 18 (85.7%) achieved ≥50% PSA reduction. Median time to treatment failure was not reached during the median follow‐up of 15.4 months. No patients experienced grade ≥3 adverse events. Although dutasteride reduced serum 3‐keto‐5α‐abiraterone concentrations, higher serum 3‐keto‐5α‐abiraterone concentrations on combination therapy were associated with a shorter time to treatment failure. HSD3B1 and SRD5A2 genotypes were associated with serum Δ4‐abiraterone and 3‐keto‐5α‐abiraterone concentrations before adding dutasteride, respectively. Time to treatment failure was longer in patients with homozygous wild‐type HSD3B1, but comparable between those with the SRD5A2 genotype. The promising outcomes of this study warrant further investigation of combination therapy in a randomized trial. Stratification by HSD3B1 and SRD5A2 genetic profiles might identify patients suitable for combination therapy. [ABSTRACT FROM AUTHOR]

Alopecia is a treatable disorder that usually occurs due to high levels of 5‐alpha dihydrotestosterone in hair follicles. To enhance the storage capacity of hair follicles and alleviate the inherent characteristics of dutasteride, 5‐alpha reductase inhibitor, a prolonged‐release nanocarrier was synthesised, and its influence on rat abdomen's skin was investigated. Results showed the lower ratio of S/Co (higher ethanol concentration) increased the hydrodynamic nanocarriers' particle size due to thermodynamic disturbance and Ostwald ripening. In contrast, an increase in surfactant through a decrease in interfacial tension resulted in smaller nanocarriers of 32.4 nm. Moreover, an increase in viscosity had an inverse correlation with the nanoemulsions' particle size. Nanocarriers containing ethanol showed less entrapment efficacy, perhaps due to the rapid dissolution of dutasteride into ethanol during nanoemulsification, while, based on Stokes' equation, the addition of ethanol resulted in smaller particle size and stability of the system. Skin permeation analysis using Franz diffusion cells showed nanocarriers could pass through the skin and release dutasteride for 6 days. In conclusion, the optimum concentration of ingredients is decisive in guaranteeing the ideal particle size, stability, and skin permeation of nanocarriers. The Present dutasteride nanocarrier would promise a prolonged and sustained‐release drug delivery system for Alopecia therapy. [ABSTRACT FROM AUTHOR]

The aim of the present study was to compare the bioavailability and to demonstrate the bioequivalence between a dutasteride‐tamsulosin 0.5 mg/0.4 mg capsule formulation and the regulatory reference drug (Combodart®, GlaxoSmithKline). A randomized, single‐blind, single‐dose, 2‐way crossover study under fasting conditions, with at least a 28‐day washout period was carried out in healthy volunteers. Plasma concentrations of drugs were determined by high‐performance liquid chromatography–tandem mass spectrometry. The pharmacokinetic analysis included maximum plasma concentration (Cmax), area under the plasma concentration–time curve (AUC) from time 0 to 72 hours, and AUC from baseline to infinity. The test formulation was considered bioequivalent if the geometric mean ratios (test/reference) were within the predetermined range of 80% to 125%. Safety and tolerability were evaluated by clinical assessment. The confidence intervals for the log‐transformed test/reference ratios for dutasteride, Cmax (95.4‐109.2) and AUC from baseline to 72 hours (93.2‐109.1), and for tamsulosin, Cmax (101.9‐119.8), AUC from baseline to the last quantifiable concentration (91.4‐106.3) and AUC from baseline to infinity (90.9‐103.3), were within the allowed limit specified by the regulatory authorities (80%‐125%). In addition, both test and reference drugs were safe and tolerated. These results demonstrated the bioequivalence of test product (Dakart®) compared with Combodart®. [ABSTRACT FROM AUTHOR]

BACKGROUND: Androgen deprivation therapy (ADT) improves outcomes in unfavorable‐risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing hormone‐releasing hormone (LHRH) agonists with a 5‐α‐reductase inhibitor (5‐ARI) would improve hormonal health‐related quality of life (HRQOL) without differentially suppressing androgen‐responsive (AR) gene expression. METHODS: Patients with localized unfavorable‐risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5‐ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long‐term LHRH agonist with RT. RNA sequencing was performed from matched pre‐/post‐ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment. RESULTS: Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow‐up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6‐month hormonal decline was 1% (oADT) versus 12% (SOC; P =.04). The 4‐year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P =.48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold‐change = 2; false‐discovery rate‐adjusted P ≤.05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling. CONCLUSIONS: For men with PCa undergoing RT, oral versus standard ADT may improve 6‐month QOL and appears to have a similar impact on androgen‐responsive gene expression. For men with localized prostate cancer undergoing radiation therapy, oral versus standard androgen deprivation therapy may improve 6‐month quality of life and appears to have a similar effect on androgen‐responsive gene expression. [ABSTRACT FROM AUTHOR]

Objectives: To prospectively evaluate the detection rate of prostate cancer, and to identify the risk factors of prostate cancer detection after a 1‐year administration of dutasteride and first negative prostate biopsy. Methods: Patients with benign prostatic hyperplasia who presented high prostate‐specific antigen levels after the first negative prostate biopsy were administered 0.5 mg dutasteride daily for 1 year. They underwent a repeat prostate biopsy after 1 year. The primary end‐point was the detection rate of prostate cancer. The secondary end‐point was the ability of prostate‐specific antigen kinetics to predict prostate cancer detection. Prostate‐specific antigen was measured before the initial prostate biopsy and at 6, 9 and 12 months after starting dutasteride. Patients were classified into a prostate cancer and a non‐prostate cancer group. Results: Prostate cancer was detected in 15 of 149 participants (10.1%). The total prostate‐specific antigen change between the prostate cancer and non‐prostate cancer group at 1 year was significantly different (P = 0.002). Although prostate‐specific antigen levels at baseline did not significantly differ between study groups (P = 0.102), prostate‐specific antigen levels at 6, 9 and 12 months were significantly different (P = 0.002, P = 0.001 and P < 0.001, respectively). The mean reduction rate of prostate‐specific antigen density between the prostate cancer and non‐prostate cancer group at 1 year was significantly different (−4.25 ± 76.5% vs −38.0 ± 28.7%, P = 0.001). Using a multivariate analysis, a >10% increase of prostate‐specific antigen density at 1 year post‐dutasteride treatment was the only predictive risk factor for prostate cancer after the first negative prostate biopsy (odds ratio 11.238, 95% confidence interval 3.112–40.577, P < 0.001). Conclusion: In the present study cohort, >10% increase in prostate‐specific antigen density represented the only significant predictive risk factor for prostate cancer diagnosis in patients with elevated prostate‐specific antigen after the first negative prostate biopsy. [ABSTRACT FROM AUTHOR]

Aims: Combination therapy of 5α‐reductase inhibitor and α‐blocker is a guideline‐endorsed therapeutic approach for patients with moderate‐to‐severe lower urinary tract symptoms or benign prostatic hyperplasia (LUTS/BPH) who are at risk of disease progression. We aimed to disentangle the contribution of clinical and demographic baseline characteristics affecting the risk of acute urinary retention or BPH‐related surgery (AUR/S) from the effect of treatment with drugs showing symptomatic and disease‐modifying properties. Methods: A time‐to‐event model was developed using pooled data from patients (n = 10 238) enrolled into six clinical studies receiving placebo, tamsulosin, dutasteride or tamsulosin‐dutasteride combination therapy. A parametric hazard function was used to describe the time to first AUR/S. Covariate model building included the assessment of relevant clinical and demographic factors on baseline hazard. Predictive performance was evaluated by graphical and statistical methods. Results: An exponential hazard model best described the time to first AUR/S in this group of patients. Baseline International Prostate Symptom Score, prostate‐specific antigen, prostate volume and maximum urine flow were identified as covariates with hazard ratio estimates of 1.04, 1.08, 1.01 and 0.91, respectively. Dutasteride monotherapy and tamsulosin‐dutasteride combination therapy resulted in a significant reduction in the baseline hazard (56.8% and 66.4%, respectively). By contrast, the effect of tamsulosin did not differ from placebo. Conclusions: Our analysis showed the implications of disease‐modifying properties of dutasteride and tamsulosin‐dutasteride combination therapy for the risk of AUR/S. It also elucidated the contribution of different baseline characteristics to the risk of these events. The use of tamsulosin monotherapy (symptomatic treatment) has no impact on individual long‐term risk. [ABSTRACT FROM AUTHOR]

Appropriate decision of prostate biopsy in men with 5α‐reductase inhibitor (5AR inhibitor) is still unclear to avoid unnecessary biopsy. We retrospectively investigated patients with initial PSA 4.0 ng/ml or more and underwent subsequent prostate biopsy following dutasteride treatment. From September 2009 to August 2018, 399 cases of benign prostate hyperplasia (BPH) were treated with dutasteride in our department. Of the total, 36 cases with elevated pre‐treatment PSA (4.0 ng/ml or more) and underwent subsequent prostate biopsy were included into this study. We evaluated PSA kinetics and changing prostate volumes (PV), and detection of prostate cancer. Overall, average PSA reduced by half at 6 months from dosing. Pre‐treatment biopsy was performed in 17 of 36 cases, and all were diagnosed as having no malignancy. After treatment, prostate cancer was detected in 15 cases by subsequent biopsy. Fourteen of 15 cases were clinically significant cancer (Gleason score 7 or more). Logistic regression analysis detected a nominal association between prostate cancer detection and three variants, PSAD, PV reduction (1–Before/After PV) and abnormal MRI findings. In addition to abnormal MRI findings and pre‐treatment of high PSAD, the case with low reduction of PV after treatment should consider performing prostate biopsy. [ABSTRACT FROM AUTHOR]

Aims: International Prostate Symptom Score (IPSS) is a marker of lower urinary tract symptoms (LUTS) deterioration or improvement in benign prostate hyperplasia (BPH). Whereas changes in IPSS relative to baseline have been used as endpoints in clinical trials, little attention has been given to the time course of symptoms. The current investigation aimed to develop a drug‐disease model to describe individual IPSS trajectories in moderate and severe BPH patients. Methods: A model‐based meta‐analytical approach was used including data from 10 238 patients enrolled into Phase III and IV studies receiving placebo, tamsulosin, dutasteride or combination therapy over a period of up to 4 years. Model predictive performance was assessed using statistical and graphical criteria. Subsequently, simulations were performed to illustrate the implications of treatment with drugs showing symptomatic and disease‐modifying properties in patients with varying disease progression rates. Results: Improvement and worsening of IPSS could be characterized by a model including a sigmoid function which disentangles drug effects from placebo and varying disease progression rates on IPSS. Mean estimate (95% confidence intervals) for the disease progression rate was 0.319 (0.271–0.411) month−1. Treatment effect on IPSS (DELTA) was found to be 0.0605, 0.0139 and 0.0310 month−1 for placebo, tamsulosin and combination therapy, respectively. In addition, it appears that individual trajectories can be clustered together into different phenotypes describing the underlying disease progression rate (i.e. slow, moderate and fast progressors). Conclusions: The availability of a drug‐disease model enables the evaluation of interindividual differences in disease progression rate, deterioration of symptoms and treatment effects on LUTS/BPH. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia (AGA) is a multifactorial disease that carries a significant psychological burden with it. Dihydrotestosterone, the main pathogenic androgen in AGA, is produced by conversion of testosterone, which is catalyzed by the 5‐alpha reductase (5‐AR) isoenzyme family. Finasteride and dutasteride are inhibitors of these enzymes. Finasteride, which is a single receptor 5‐alpha reductase inhibitor (5‐ARI), acts by blocking dihydrotestosterone (DHT). Dutasteride, a dual receptor DHT blocker, has a higher potency than its predecessor, finasteride. This review corroborates the evidence of superiority of dutasteride over finasteride, and its comparable safety profile concerning fertility, teratogenicity, neurotoxicity, and hepatotoxicity. [ABSTRACT FROM AUTHOR]

An analytical procedure based on ultra‐performance liquid chromatography‐mass spectrometry was developed to screen and to confirm dutasteride and its metabolites in human urine. Sample preparation included an enzymatic hydrolysis followed by solid‐phase extraction using the strong cation exchange cartridges OASIS® MCX. The chromatographic separation was carried out on C18 column, employing as mobile phases ultra purified water and acetonitrile, both containing 0.1% formic acid. Detection was achieved using a triple quadrupole as a mass spectrometric analyzer, with positive ion electrospray ionization and multiple reaction monitoring as acquisition mode. The analytical procedure developed was validated according to ISO 17025 and World Anti‐Doping Agency guidelines. The extraction efficiency was estimated to be greater than 75% for both dutasteride and its hydroxylated metabolites. Detection capability was determined in the range of 0.1–0.4 ng/mL. Specificity and repeatability of the relative retention times (CV% < 0.5) and of the relative abundances of the characteristic ion transitions selected (CV% < 10) were confirmed to be fit for purpose to ensure the unambiguous identification of dutasteride and its metabolites in human urine. The developed method was used to characterize the urinary excretion profile of dutasteride after both chronic and acute administration of therapeutic doses. After chronic administration, dutasteride and its hydroxylated metabolites were easily detected and confirmed. After acute administration, instead, only the two hydroxylated metabolites were detected for 3–4 days. [ABSTRACT FROM AUTHOR]

Objective: To investigate the use of 5α‐reductase inhibitors (5ARIs) and α‐blockers among men with benign prostatic hyperplasia (BPH) in relation to prostate cancer (PCa) incidence, severity and mortality. Patients and Methods: A retrospective 20‐year cohort study in men residing in Saskatchewan, aged 40–89 years, with a BPH‐coded medical claim between 1995 and 2014, was conducted. Cox proportional hazards regression was used to compare incidence of PCa diagnosis, metastatic PCa, Gleason score 8–10 PCa, and PCa mortality among 5ARI users (n = 4 571), α‐blocker users (n = 7 764) and non‐users (n = 11 677). Results: In comparison with both non‐users and α‐blocker users, 5ARI users had a ~40% lower risk of a PCa diagnosis (11.0% and 11.4% vs 5.8%, respectively), and α‐blocker users had an 11% lower risk of a PCa diagnosis compared with non‐users. Overall, the incidence of metastatic PCa and PCa mortality was not significantly different among 5ARI or α‐blocker users compared with non‐users (adjusted hazard ratios [HR] of metastatic PCa: 1.12 and 1.13, respectively, and PCa mortality: 1.11 and 1.18, respectively, P > 0.05 for both drugs), but both 5ARI and a‐blocker users had ~30% higher risk of Gleason score 8–10 cancer, adjusted HR 1.37, 95% confidence interval [CI] 1.03–1.82, P = 0.03, and adjusted HR 1.28, 95% CI 1.03–1.59, P = 0.02, respectively compared with non‐users. Conclusion: The use of 5ARIs was associated with lower risk of PCa diagnosis, regardless of comparison group. Risk of high grade PCa was higher among both 5ARI users and α‐blocker users compared with non‐users; however, this did not translate into higher risk of PCa mortality. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effectiveness and safety of dutasteride 0.5 mg + tamsulosin 0.2 mg combination compared with tamsulosin 0.2 mg in Asian men with moderate‐to‐severe benign prostatic hyperplasia. Methods: A 4‐week, single‐blind, placebo, run‐in was followed by a 2‐year double‐blind randomized controlled trial in men age ≥50 years with symptomatic benign prostatic hyperplasia, International Prostate Symptom Score ≥12, prostate volume ≥30 cc, prostate‐specific antigen ≥1.5 and ≤10 ng/mL, peak urinary flow >5 and ≤15 mL/s, and voided volume of ≥125 mL. Participants were randomized to oral daily dutasteride 0.5 mg + tamsulosin 0.2 mg combination or tamsulosin 0.2 mg. The primary efficacy end‐point was change in International Prostate Symptom Score at year 2. Results: Data from 607 participants showed a significant reduction in International Prostate Symptom Score (P < 0.05) at month 24, along with greater improvements (P ≤ 0.006) in peak urinary flow at every assessment and significant prostate volume reduction at months 12 and 24 (P < 0.001) in the combination group. Combination therapy was associated with a significant reduction in the risk of acute urinary retention or benign prostatic hyperplasia‐related surgery (P = 0.012), primarily due to a significant reduction in the risk of acute urinary retention (P = 0.005). The safety and tolerability profile of combination therapy was consistent with the known profiles for the individual monotherapies. Conclusions: Dutasteride 0.5 mg + tamsulosin 0.2 mg combination therapy showed better clinical outcomes than tamsulosin 0.2 mg monotherapy, making it an effective and safe treatment option for Asian men with moderate‐to‐severe benign prostatic hyperplasia. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a computer vision‐based approach applied to haematoxylin and eosin (H&E) prostate biopsy images can distinguish dutasteride‐treated tissue from placebo, and identify features associated with degree of responsiveness to 5α‐reductase inhibitor (5ARI) therapy. Subjects and Methods: Our study population comprised 100 treatment‐adherent men without prostate cancer assigned to dutasteride or placebo in the REDUCE trial, who had slides available from mandatory year‐4 biopsies. Half of the men also provided slides from a year‐2 biopsy. We obtained 20× whole‐slide images and used specialized software to generate a library of 1 300 epithelial and stromal features from objects comprising superpixels and several types of nuclei, including spatial relations among objects between and within each hierarchical level. We used penalized logistic regression and fivefold cross‐validation to find optimal combinations of histological features in the year‐4 biopsies. Feature data from the year‐2 biopsies were fitted to a final model for independent validation. Two pathologists, blinded to treatment, scored each image for focal atrophy and histological features previously linked to 5AR1 treatment. Results: Consensus classification by pathologists obtained a discrimination accuracy equivalent to chance. A 21‐feature computer vision model gave a cross‐validation area under the curve of 0.97 (95% confidence interval [CI] 0.95–0.99) in the year‐4 biopsies and 0.79 (95% CI: 0.65–0.92) in the set‐aside year‐2 biopsies. Histology scores were not correlated with change in prostate‐specific antigen level, serum dihydrotestosterone level or gland volume. Key features associated with dutasteride treatment included greater shape and colour uniformity in stroma, irregular clustering of epithelial nuclei, and greater variation in lumen shape. Conclusion: The present findings show that a computer vision approach can detect subtle histological effects attributable to dutasteride, resulting in a continuous measure of responsiveness to the drug that could eventually be used to predict individual patient response in the context of BPH treatment or cancer chemoprevention. [ABSTRACT FROM AUTHOR]

Abstract: Treatment with 5α‐reductase inhibitors has been associated with sexual adverse events such as impotence (erectile dysfunction) and decreased libido. The primary objective of this study was to evaluate adverse events related to sexual function, based on their frequency, duration, persistence and associated treatment discontinuations, in men treated with dutasteride for androgenetic alopecia. Participants were randomized to receive double‐blind dutasteride 0.5 mg or placebo once daily for 24 weeks, followed by open‐label dutasteride 0.5 mg for an additional 24 weeks. Sexual adverse events were followed up until resolution or for up to 24 weeks after the last dose. Overall, 117 men, 23–50 years of age, were randomized. The incidence of sexual adverse events was approximately twofold higher in the dutasteride group (16%) than the placebo group (8%) during the double‐blind period; the overall incidence of sexual adverse events was lower (5%) during the open‐label period. All adverse events were mild to moderate in severity and considered treatment‐related. The adverse events resolved while on study treatment or after the end of treatment and did not lead to treatment discontinuation. A limitation of this study was the small sample size. The sexual adverse events of impotence, decreased libido and ejaculation disorders reported in this study were expected and reversible. [ABSTRACT FROM AUTHOR]

Background: T2 -weighted imaging (T2 -WI) information has been used in a qualitative manner in the assessment of prostate cancer. Quantitative derivatives (T2 relaxation time) can be generated from T2 -WI. These outputs may be useful in helping to discriminate clinically significant prostate cancer from background signal.Purpose/hypothesis: To investigate changes in quantitative T2 parameters in lesions and noncancerous tissue of men on active surveillance for prostate cancer taking dutasteride 0.5 mg or placebo daily for 6 months.Study Type: Retrospective.Population/subjects: Forty men randomized to 6 months of daily dutasteride (n = 20) or placebo (n = 20).Field Strength/sequence: Multiparametric 3T MRI at baseline and 6 months. This included a multiecho MR sequence for quantification of the T2 relaxation times, in three regions of interest (index lesion, noncancerous peripheral [PZ] and transitional [TZ] zones). A synthetic signal contrast (T2 Q contrast) between lesion and noncancerous tissue was assessed using quantitative T2 values. Signal contrast was calculated using the T2 -weighted sequence (T2 W contrast).Assessment: Two radiologists reviewed the scans in consensus according to Prostate Imaging Reporting and Data System (PI-RADS v. 2) guidelines.Statistical Tests: Wilcoxon and Mann-Whitney U-tests, Spearman's correlation.Results: When compared to noncancerous tissue, shorter T2 values were observed within lesions at baseline (83.5 and 80.5 msec) and 6 months (81.5 and 81.9 msec) in the placebo and dutasteride arm, respectively. No significant differences for T2 W contrast at baseline and after 6 months were observed, both in the placebo (0.40 [0.29-0.49] vs. 0.43 [0.25-0.49]; P = 0.881) and dutasteride arm (0.35 [0.24-0.47] vs. 0.37 [0.22-0.44]; P = 0.668). There was a significant, positive correlation between the T2 Q contrast and the T2 W contrast values (r = 0.786; P < 0.001).Data Conclusion: The exposure to antiandrogen therapy did not significantly influence the T2 contrast or the T2 relaxation values in men on active surveillance for prostate cancer.Level Of Evidence: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1646-1653. [ABSTRACT FROM AUTHOR]

Abstract: The relative bioavailabilities of dutasteride/tamsulosin hydrochloride 0.5 mg/0.2 mg fixed‐dose combination (FDC) capsules compared with coadministered reference products (1 dutasteride 0.5‐mg capsule [Avodart®] + 1 tamsulosin hydrochloride 0.2‐mg orally disintegrating tablet [Harnal D®]) were investigated in 2 clinical trials under fasted and fed conditions (ClinicalTrials.gov NCT02184585 and NCT02509104). Both trials were open‐label, randomized, single‐dose, crossover studies in healthy male adults aged 18‐65 years. Trial 1 evaluated 2 formulations (FDC1 and FDC2), and trial 2 evaluated a third formulation (FDC3). The primary end points were dutasteride area under the concentration‐time curve from time 0 to t (AUC(0‐t)) and peak plasma concentration (Cmax) and tamsulosin AUC(0‐∞), AUC(0‐t), and Cmax. The formulations were considered to be bioequivalent if the 90%CIs for the geometric mean ratios for each end point were within the range of 0.80‐1.25. For FDC1 in trial 1, bioequivalence criteria were not met for dutasteride Cmax or AUC in the fasted state or for tamsulosin Cmax in the fasted or fed states. For FDC2 in trial 1, all bioequivalence criteria were met except for tamsulosin Cmax in the fasted state. For FDC3 in trial 2, bioequivalence criteria were met for all dutasteride and tamsulosin end points in both the fed and fasted states. Safety profiles were similar for all FDC formulations and combination treatments. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: A recent regulatory warning and case reports have described the development of muscle complications with the use of 5‐α reductase inhibitors (5ARIs). We wished to determine if there was a link between rhabdomyolysis and 5ARI usage. Methods: We used a matched cohort design and linked administrative data from the province of Ontario, Canada, to investigate the risk of rhabdomyolysis in men using either finasteride or dutasteride. A total of 99 covariates were measured. We identified 93 197 men ≥66 years of age who initiated a new prescription for a 5ARI, and they were matched using a propensity score to an equal number of men not prescribed a 5ARI. Results: New initiation of 5ARIs was not associated with a significantly increased risk of rhabdomyolysis (hazard ratio [HR] 1.21, 95% confidence interval [CI], 1.00‐1.48, P = .06). When we examined the risk of rhabdomyolysis in the year prior to the initiation of a 5ARI, we found that men who would go on to use a 5ARI in the future had an elevated risk of rhabdomyolysis even prior to starting the medication (HR 1.31, 95% CI, 1.05‐1.64, P = .01). Our secondary outcome of myositis and myopathy was significantly higher among 5ARI users (HR 1.63, 95% CI, 1.48‐1.80, P < .01), and this risk was not present prior to 5ARI usage. Conclusion: 5‐α reductase inhibitors do not appear to be associated with the development of rhabdomyolysis; however, they may be associated with an increased risk of myopathy and myositis. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the effects of dutasteride on serum hormone levels and aging male symptoms in patients with benign prostatic enlargement. Methods: The present prospective study was carried out in 110 symptomatic benign prostatic enlargement patients treated with daily administration of 0.5 mg dutasteride. We analyzed serum hormonal levels and aging related symptoms using a validated Aging Male Symptom questionnaire at baseline and after 3 months of dutasteride treatment. Results: The mean total testosterone, free testosterone and luteinizing hormone levels after dutasteride treatment were approximately 20% higher than those at baseline. The percentage increases in total and free testosterone levels were negatively correlated with these baseline levels. Baseline age, levels of total testosterone and free testosterone, and the changes in the rate of luteinizing hormone after dutasteride treatment tended to be correlated with an increase in the rate of total testosterone and free testosterone after dutasteride treatment. In a subgroup of 26 patients with moderate‐to‐severe aging male symptoms, poor morning erection and free testosterone levels <8.5 pg/mL, total aging male symptoms, and somatic symptoms scores significantly decreased after dutasteride treatment with an increase of total and free testosterone. Conclusions: The increase of endogenous free testosterone and total testosterone by dutasteride might bring additional benefits of improvement of aging male‐related symptoms, especially in patients with lower free testosterone baseline levels and moderate‐to‐poor aging‐related symptoms. [ABSTRACT FROM AUTHOR]

AIMS The ultrasound assessment of bladder wall thickness (BWT) and intravesical prostatic protrusion (IPP) have emerged as a non-invasive, inexpensive, time-saving alternatives to pressure-flow studies to assess benign prostatic obstruction (BPO). Aim of our study was to evaluate the effect on detrusor mass of dutasteride add-on therapy in men with lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE). METHODS A consecutive series of BPE patients with a prostate volume (PV) ≥30 mL and an international prostate symptoms score (IPSS) ≥8 not satisfied with Tamsulosin monotherapy were enrolled. Free maximum flow (Qmax), PV, BWT, and IPP were recorded at baseline and at 24 weeks follow-up. RESULTS Overall, 27 men were enrolled. Dutasteride significantly improved LUTS (−46.7%; P = 0.001) and Qmax (+18.7%; P = 0.001) and reduced PV (−13%; P = 0.002), BWT (−40.3%; P = 0.001), and IPP (−14.9%; P = 0.015). At baseline, based on BWT ≥5 mm and an IPP >10 mm, 13/27 (48%) and 15/27 (55%) patients were defined at risk for BPO, respectively; while after 24 weeks of treatment they were 3/27 (11.1%) and 11/27 (40%), respectively. CONCLUSIONS Dutasteride add-on therapy significantly reduced IPP and detrusor mass and was effective in improving LUTS in patients with BPE not satisfied with αBs monotherapy. The possible role of BWT and IPP as proxies of medical treatment outcomes should be confirmed by further studies. [ABSTRACT FROM AUTHOR]

Objectives To assess the efficacy of dutasteride add-on therapy for patients with benign prostatic hyperplasia ( BPH) and lower urinary tract symptoms ( LUTS) with small prostates who have been treated with α-blocker therapy for >3 months. Methods A total of 110 men with clinical BPH were enrolled. There were 17 and 93 subjects with a prostate volume ( PV) <30 and ≥30 mL, respectively. All subjects had been treated with α-blocker therapy for >3 months. Subjective and objective clinical variables were assessed using the total International Prostate Symptom Score ( IPSS-T), IPSS quality of life ( IPSS-QoL), IPSS voiding subscore ( IPSS-V), IPSS storage subscore ( IPSS-S), overactive bladder symptom score ( OABSS), PV, prostate specific antigen ( PSA) level, post-void residual ( PVR), and maximum flow rate ( Qmax). These variables were assessed at baseline and every 3 months for 1 year. Results In the small prostate group, IPSS-T and IPSS-V showed improvements from baseline at 6 and 9 months, storage subscore at 6 months, and OABSS at 3 months, but no sustained improvements were observed. During the study period, only the IPSS QoL scores did not show any improvement. Conversly, dutasteride was significantly effective at improving IPSS-T, IPSS-V, IPSS-S, and IPSS-QoL scores throughout the study period in the large prostate BPH group. PSA levels and PV significantly decreased in both groups throughout the study. Conclusions Benign prostatic hyperplasia in LUTS patients with small prostates did not show a sustainable benefit from the addition of dutasteride to α-blocker therapy. [ABSTRACT FROM AUTHOR]

Despite their efficacy in the treatment of benign prostatic hyperplasia, the popularity of inhibitors of 5α-reductase (5 ARIs) is limited by their association with adverse sexual side effects. The aim of this study was to review and meta-analyze currently available randomized clinical trials evaluating the rate of sexual side effects in men treated with 5 ARIs. An extensive Medline Embase and Cochrane search was performed including the following words: 'finasteride', 'dutasteride', 'benign prostatic hyperplasia'. Only placebo-controlled randomized clinical trials evaluating the effect of 5 ARI in subjects with benign prostatic hyperplasia were considered. Of 383 retrieved articles, 17 were included in this study. Randomized clinical trials enrolled 24,463 in the active and 22,270 patients in the placebo arms, respectively, with a mean follow-up of 99 weeks and mean age of 64.0 years. No difference was observed between trials using finasteride or dutasteride as the active arm considering age, trial duration, prostate volume or International Prostatic Symptoms Score at enrollment. Overall, 5 ARIs determined an increased risk of hypoactive sexual desire [ OR = 1.54 (1.29; 1.82); p < 0.0001] and erectile dysfunction [ OR = 1.47 (1.29; 1.68); p < 0.0001]. No difference between finasteride and dutasteride regarding the risk of hypoactive sexual desire and erectile dysfunction was observed. Meta-regression analysis showed that the risk of hypoactive sexual desire and erectile dysfunction was higher in subjects with lower Qmax at enrollment and decreased as a function of trial follow-up. Conversely, no effect of age, low urinary tract symptom or prostate volume at enrollment as well as Qmax at end-point was observed. In conclusion, present data show that the use of 5 ARI significantly increases the risk of erectile dysfunction and hypoactive sexual desire in subjects with benign prostatic hyperplasia. Patients should be adequately informed before 5 ARIs are prescribed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether 5α-reductase inhibitors (5-ARIs) affect the discrimination between low-grade prostate cancer and benign tissues on multiparametric MRI (mpMRI). Twenty men with biopsy-proven Gleason 3 + 3 prostate cancer and 3 T mpMRI were studied. Ten patients (Tx) had been receiving 5-ARIs for at least a year at scan time. Ten untreated patients (Un) were matched to the treated cohort. For each subject two regions of interest representing cancerous and benign tissues were drawn within the peripheral zone of each prostate, MR measures evaluated, and cancer contrast versus benign (contrast = (MRTumor − MRHealthy)/MRHealthy) calculated. Decreased cancer contrast was noted on T2-weighted images: 0.4 (Un) versus 0.3 (Tx). However, for functional MR measures, a better separation of cancerous and benign tissues was observed in the treated group. Cancer contrast on high- b diffusion-weighted imaging (DWI) was 0.61 (Un) versus 0.99 (Tx). Logistic regression analysis yielded higher AUC (area under the curve) values for distinguishing cancerous from benign regions in treated subjects on high- b DWI (0.71 (Un), 0.94 (Tx)), maximal enhancement slope (0.95 (Un), 1 (Tx)), peak enhancement (0.84 (Un), 0.93 (Tx)), washout slope (0.78 (Un), 0.99 (Tx)), Ktrans (0.9 (Un), 1 (Tx)), and combined measures (0.86 (Un), 0.99 (Tx)). Coefficients of variation for MR measures were lower in benign and cancerous tissues in the treated group compared with the untreated group. This study's results suggest an increase in homogeneity of benign and malignant peripheral zone prostatic tissues with 5-ARI exposure, observed as reduced variability of MR measures after treatment. Cancer discrimination was lower with T2-weighted imaging, but was higher with functional MR measures in a 5-ARI-treated cohort compared with controls. [ABSTRACT FROM AUTHOR]

We evaluated the effects of dutasteride on the genitourinary tract using fifteen 8-week-old male Sprague-Dawley rats. Animals were divided into three groups comprising five animals each and treated as follows. Group A was a control group, members of Group B received oral administration of dutasteride 0.1 mg/kg/day from the age of 8 to 16 weeks, and members of Group C were castrated at the age of 8 weeks. All rats were killed at the age of 16 weeks for the sample collection of blood, bladder, prostate, seminal vesicles, and penis. Then, we evaluated the pathological examination for evaluating the tissue fibrosis and hormonal receptor expression. The results showed that the mean size of the prostate and seminal vesicles was smaller in Group B and Group C than in Group A. Serum and tissue concentrations of both testosterone and dihydrotestosterone were remarkably reduced in serum and all tissues in Group C compared with Group A. On the other hand, in Group B, only dihydrotestosterone was reduced in serum and penis. Histopathological examination revealed that Group C showed statistically significant histological changes, such as an increase in fibrotic tissue in the bladder, prostate, and penis. Similarly, Group B showed fibrotic changes in the prostate and penis compared with the Group A. Immunofluorescent staining revealed that the androgen receptor was more strongly expressed than the estrogen receptor beta in Group A. On the other hand, in Group C, weak expression of the androgen receptor and strong expression of the estrogen receptor beta was noted. In Group B, these changes were noted in the prostate and penis. These findings suggest that dutasteride cause morphological changes not only in prostate but also in penis. These changes are associated with altered expression patterns of androgen receptor and estrogen receptor. [ABSTRACT FROM AUTHOR]

Sixty-two patients with benign prostate hyperplasia ( BPH) who were being treated with dutasteride participated in this study. Prostate volume, uroflowmetry, blood tests, the International Prostate Symptom Score ( IPSS) and International Index of Erectile Function ( IIEF-5) were determined before and 1, 3 and 12 months after the treatment with dutasteride. Patients were divided into two groups based on changes in serum testosterone after 1 month: Group A (>20% increase; n = 33) or Group B (<20% increase; n = 29). Serum free-testosterone levels were 20.4% higher after 1 month and remained constant thereafter. When Groups A and B were compared, baseline free-testosterone levels were significantly lower in Group A, IPSS QOL was significantly better in Group A at 3 and 12 months, and no significant differences were observed in uroflowmetry, prostate volume, IPSS or IIEF-5. A univariate analysis identified serum free-testosterone levels and the IPSS storage symptom subscore as significant factors influencing IPSS QOL at 12 months, and only the IPSS storage symptom subscore appeared to be independently related to IPSS QOL. These results indicate that dutasteride increases serum free-testosterone levels in BPH patients, particularly with low baseline free-testosterone levels, and the increase in free-testosterone may have further add-on impacts on their urinary tract symptoms. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia is an androgen-induced pattern of progressive hair loss, which occurs in genetically predisposed people. This study aimed to determine long-term safety, tolerability and efficacy of dutasteride 0.5 mg, an inhibitor of 5-α-reductase, in Japanese male patients with androgenetic alopecia. This was a multicenter, open-label, prospective outpatient study (clinicaltrials.gov NCT01831791, GSK identifier ARI114264) in which patients took dutasteride 0.5 mg p.o. once daily for 52 weeks. Primary end-points included adverse event assessment, incidence of drug-related adverse event and premature discontinuations. Secondary end-points included hair growth, hair restoration and global improvement in hair. A total of 120 patients were enrolled, of whom 110 completed 52 weeks of treatment. Nasopharyngitis, erectile dysfunction and decreased libido were the most frequently reported adverse events and most adverse events were mild. Drug-related adverse events were reported with an incidence of 17%, none of which led to study withdrawal. Hair growth (mean target area hair count at week 52), hair restoration (mean target area hair width at week 52) and global appearance of hair (mean of the median score at week 52) improved from baseline during the study. As a potential future treatment option for male androgenetic alopecia, dutasteride 0.5 mg exhibited long-term safety, tolerability and efficacy within this study population. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effect of tamsulosin (0.2 mg) on the pharmacokinetics of dutasteride (0.5 mg) in a group of healthy Chinese male volunteers. This was an open-label, single-sequence, 3-period, drug-drug interaction phase 1 study. Twenty-four healthy Chinese male volunteers were enrolled and administered a single dose of 0.5 mg dutasteride and, following a 28- to 30-day washout period, 0.2 mg tamsulosin once daily for 7 days. On day 5, subjects received 0.2 mg tamsulosin coadministered with 0.5 mg dutasteride. Serum dutasteride and tamsulosin concentrations were monitored. In the presence or absence of tamsulosin, there were no apparent changes in dutasteride AUC and Cmax. Adverse events reported were mild to moderate in intensity and resolved by the end of the study. In healthy Chinese male volunteers, tamsulosin 0.2 mg at steady state had no apparent effect on dutasteride pharmacokinetics. Dutasteride and tamsulosin when administered alone or in combination were well tolerated. [ABSTRACT FROM AUTHOR]

Objective To investigate whether a fixed-dose combination ( FDC) of 0.5 mg dutasteride and 0.4 mg tamsulosin is more effective than watchful waiting with protocol-defined initiation of tamsulosin therapy if symptoms did not improve ( WW-All) in treatment-naïve men with moderately symptomatic benign prostatic hyperplasia ( BPH) at risk of progression. Patients and Methods This was a multicentre, randomised, open-label, parallel-group study ( NCT01294592) in 742 men with an International Prostate Symptom Score ( IPSS) of 8-19, prostate volume ≥30 mL and total serum PSA level of ≥1.5 ng/mL. Patients were randomised to FDC (369 patients) or WW-All (373) and followed for 24 months. All patients were given lifestyle advice. The primary endpoint was symptomatic improvement from baseline to 24 months, measured by the IPSS. Secondary outcomes included BPH clinical progression, impact on quality of life ( QoL), and safety. Results The change in IPSS at 24 months was significantly greater for FDC than WW-All (-5.4 vs −3.6 points, P < 0.001). With FDC, the risk of BPH progression was reduced by 43.1% ( P < 0.001); 29% and 18% of men in the WW-All and FDC groups had clinical progression, respectively, comprising symptomatic progression in most patients. Improvements in QoL ( BPH Impact Index and question 8 of the IPSS) were seen in both groups but were significantly greater with FDC ( P < 0.001). The safety profile of FDC was consistent with established profiles of dutasteride and tamsulosin. Conclusion FDC therapy with dutasteride and tamsulosin, plus lifestyle advice, resulted in rapid and sustained improvements in men with moderate BPH symptoms at risk of progression with significantly greater symptom and QoL improvements and a significantly reduced risk of BPH progression compared with WW plus initiation of tamsulosin as per protocol. [ABSTRACT FROM AUTHOR]

Objective To investigate if short-term treatment with dutasteride (8 weeks) before bipolar transurethral resection of the prostate ( B- TURP) can reduce intraoperative bleeding, as dutasteride a dual 5α-reductase inhibitor (5- ARI) blocks the conversion of testosterone into its active form dihydrotestosterone ( DHT), and reduces prostate volume and prostate-specific antigen ( PSA) levels, while increasing urinary flow rate. Patients and Methods In all, 259 patients were enrolled and randomised to two groups: Group A, receiving placebo and Group B, receiving dutasteride (0.5 mg daily for 8 weeks). Blood samples were taken before and after B- TURP for serum chemistry evaluation. In particular we evaluated blood parameters associated with blood loss [haemoglobin ( Hb) and haematocrit ( Ht)] and prostate vascularity [vascular endothelial growth factor ( VEGF) immunoreactivity and microvessel density ( MVD) using cluster of differentiation 34 ( CD34) immunoreactivity]. Results Total testosterone, DHT, PSA level and prostate volume were evaluated and with the exception of DHT and PSA level there was no statistically significant differences between the groups. When comparing changes in Hb and Ht between Group A and Group B before and after B- TURP, there was a statistically significant difference only in patients with large prostates of ≥50 mL (Δ Hb 3.86 vs 2.05 g/dL and Δ Ht 4.98 vs 2.64%, in Groups A and B, respectively). There was no significant difference in MVD and VEGF index in prostates of <50 mL, conversely in large prostates the difference become statistically significant. Conclusions Dutasteride was able to reduce operative and perioperative bleeding only in patients with large prostates (≥50 mL) that underwent B- TURP. Our findings are confirmed by Hb and Ht values reported before and after the B- TURP and reductions in the molecular markers for VEGF and CD34 in the dutasteride-treated specimens. [ABSTRACT FROM AUTHOR]

Objectives To investigate factors influencing the degree of difficulty in finding and maintaining an appropriate plane on the surgical capsule of the prostate during holmium laser enucleation of the prostate. Methods A total of 116 men undergoing holmium laser enucleation of the prostate for benign prostate hyperplasia between January 2010 and September 2013 at our hospital were included in this analysis. The degree of difficulty in finding and maintaining the plane of the surgical capsule of the prostate was retrospectively evaluated and graded by using video-based analysis according to newly defined criteria (grade I, least difficult; grade IV, most difficult). Factors influencing the degree of difficulty were investigated. Results Video analysis was possible in 99 of 116 patients. Decapsulation difficulty in decapsulation was deemed as being grade I in 32 patients, grade II in 31 patients, grade III in 20 patients and grade IV in 16 patients. Preoperative dutasteride therapy was the only factor associated with an increasing level of difficulty in decapsulation during holmium laser enucleation of the prostate. Conclusions Although preoperative dutasteride therapy effectively reduces intraoperative blood loss, surgeons with limited experience should be careful with the use of dutasteride, because its administration might increase surgical difficulty during holmium laser enucleation of the prostate. [ABSTRACT FROM AUTHOR]

We investigate the impact of dutasteride on prostate specific antigen ( PSA) and prostate volume in men receiving testosterone (T) therapy. Twenty-three men on stable dose T therapy were randomised to receive either dutasteride or placebo for 12 months. Serum levels of PSA, T and dihydrotestosterone ( DHT) and responses to the International Index of Erectile Function ( IIEF) and Male Sexual Health Questionnaire ( MSHQ) questionnaires were determined at baseline and at 3, 6, 9 and 12 months. Prostate volume ( PV) was measured using transrectal ultrasound ( TRUS) at baseline and again after 12 months. A total of 22 men (mean age 57.3) completed the study, with 11 men receiving placebo and 11 receiving dutasteride. Men receiving dutasteride had a significant decrease in PSA (−0.46 ± 0.81 ng ml−1; P = 0.04) and in PV (−6.65 ± 11.0%; P = 0.03) from baseline over 12 months. DHT decreased significantly for men on dutasteride compared with men receiving placebo ( P = 0.02). When compared with men who received placebo, men who received dutasteride demonstrated nonsignificant trends towards decreased PSA (−0.46 versus 0.21 ng ml−1; P = 0.11), PV (−6.65% versus 3.4%; P = 0.08) and MSHQ scores (−10.2 versus 5.6; P = 0.06). Dutasteride reduces PSA and PV for men on T therapy, but perhaps less so than in men without T therapy. [ABSTRACT FROM AUTHOR]

A 46-year-old premenopausal woman presented with familial frontal fibrosis alopecia affecting the temples bilaterally. The diagnosis was confirmed histologically. Her past history included rheumatoid arthritis treated with hydroxychloroquine 400 mg daily and methotrexate 20 mg weekly. Serial intralesional injections of triamcinolone did not limit the progression of hair loss. Treatment with dutasteride 0.1 mg daily and minoxidil 1 mg daily stabilised hair loss and artificial fibre hair transplantation initially led to a satisfactory cosmetic outcome. Unfortunately, the patient developed implant folliculitis uncontrolled by antibiotics, necessitating the removal of the fibres 12 months post-transplantation. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the correlation of clinical and urodynamic parameters with bladder vascular resistance before and after dutasteride treatment in patients with lower urinary tract symptoms associated with benign prostatic enlargement. Methods A prospective study was conducted in 30 consecutive patients with benign prostatic enlargement who had not been satisfied with alpha-adrenergic antagonist monotherapy. Before and 24 weeks after dutasteride add-on treatment, we assessed International Prostate Symptom Score ( IPSS), prostate volume ( PV), urodynamic study and contrast-enhanced color Doppler ultrasonography to measure bladder vascular resistive index ( RI). Results Twenty-four weeks after dutasteride, PV significantly decreased from 68 ± 29 to 48 ± 28 mL ( P < 0.001), and there was significant improvement of IPSS (from 18.8 ± 7.7 to 13.4 ± 7.2, P < 0.001). Urgency score of IPSS was also significantly improved from 2.3 ± 1.9 to 1.4 ± 1.4 ( P < 0.01) after dutasteride. On pressure-flow study, bladder outlet obstruction index ( BOOI) (from 58 ± 36 to 38 ± 27, P < 0.001) and detrusor pressure at Qmax ( PdetQmax) (from 73 ± 34 to 54 ± 25 cmH2O, P < 0.001) were significantly improved. RI significantly decreased after dutasteride (from 0.548 ± 0.069 to 0.486 ± 0.064, P < 0.001). In 20 patients with persistent urgency after dutasteride, RI was less improved than in another 10 patients without urgency (change of RI 0.045 ± 0.091 vs. 0.096 ± 0.042, P < 0.05). Post-treatment BOOI and PdetQmax in patients with persistent urgency was significantly higher than in those without urgency after dutasteride ( BOOI: 46 ± 28 vs. 24 ± 20, P < 0.05, PdetQmax: 62 ± 26 vs. 40 ± 17 cmH2O, P < 0.01). Conclusions Reduction of obstruction and improvement of bladder ischemia might play an important role in a beneficial impact of dutasteride on overactive bladder symptoms. [ABSTRACT FROM AUTHOR]

Objectives To examine urinary nerve growth factor before and after dutasteride treatment, and to analyze correlations between clinical parameters and change of urinary nerve growth factor in patients with benign prostatic enlargement. Methods We prospectively studied 30 patients with benign prostatic enlargement who had not been satisfied with α-adrenergic antagonist monotherapy for more than 3 months. Before and 24 weeks after dutasteride add-on treatment, we assessed International Prostate Symptom Score, prostatic volume, filling cystometry and pressure-flow study. Urinary nerve growth factor was measured by enzyme-linked immunosorbent assay, and normalized to the urinary creatinine (nerve growth factor/creatinine) before and 24 weeks after dutasteride add-on treatment. Results In baseline characteristics before dutasteride, there was no significant correlation between urinary nerve growth factor/creatinine and any clinical parameters including age, International Prostate Symptom Score, prostatic volume, presence of detrusor overactivity, detrusor pressure at maximum flow rate, bladder outlet obstruction index or bladder contractility index. Dutasteride significantly reduced prostatic volume (from 68 ± 31 mL to 49 ± 28 mL) and improved International Prostate Symptom Score (from 17.2 ± 8.7 to 13.1 ± 6.8), storage (from 8.0 ± 4.3 to 6.0 ± 2.9) and voiding symptom subscore of International Prostate Symptom Score (from 9.3 ± 5.7 to 7.1 ± 4.5). In urodynamic study, detrusor pressure at maximum flow rate (from 77 ± 32 cmH2O to 59 ± 24 cmH2O) and bladder outlet obstruction index (from 62 ± 32 to 42 ± 27) were significantly decreased after dutasteride treatment. Urinary nerve growth factor/creatinine was significantly decreased after dutasteride from 2.61 ± 2.50 to 1.64 ± 1.68. The change of urinary nerve growth factor/creatinine significantly correlated only with the change of prostatic volume ( r = 0.38) and bladder outlet obstruction index ( r = 0.36). Conclusions Urinary nerve growth factor decreases in association with reduction of prostatic volume and relief of bladder outlet obstruction. Urinary nerve growth factor might be useful as a biomarker to monitor the improvement of bladder outlet obstruction in patients with benign prostatic enlargement. [ABSTRACT FROM AUTHOR]

Objective To investigate the hypothesis that 5-alpha-reductase inhibitors exert early ameliorative effects on voiding and storage symptoms in men with lower urinary tract symptom-associated benign prostatic hyperplasia. Methods This was a prospective study involving the participation of eight outpatient clinics in Chiba Prefecture, Japan. The patients received dutasteride (0.5 mg) once daily orally for 24 weeks as an add-on to their ongoing therapy with an alpha-1 blocker. The study patients recorded their urinary symptoms every day for 14 days after starting dutasteride. The International Prostate Symptom Score, prostate volume, uroflowmetry results, and residual urine volume were checked at 3 and 6 months after starting dutasteride. Results A total of eighty-eight patients participated in the present study; 74 were eligible for analysis of the early effects of dutasteride. The median age was 69.6 years (range 54-89), the median prostate volume was 50.3 mL (range 24.7-103.3) and the median International Prostate Symptom Score was 17.6 (range 8-35). The proportion of patients with International Prostate Symptom Score improvements (≥3 points, or ≥25%) or 3 points or more decreased International Prostate Symptom Score were defined effective, 37 (50.0%) and 47 (63.5%) experienced improvement at 1 month after administration, respectively. Conclusion This is the first prospective clinical study to show the early beneficial effects of 5-alpha-reductase inhibitors for lower urinary tract symptom-associated benign prostatic hyperplasia. Patients with severe symptoms were found to be responsive to dutasteride. The influence of the placebo effect was not denied. Further study is necessary. [ABSTRACT FROM AUTHOR]

Objective To examine, using post hoc analysis, the influence of baseline variables on changes in international prostate symptom score ( IPSS), maximum urinary flow rate ( Qmax) and IPSS quality of life ( QoL) in patients with moderate-to-severe lower urinary tract symptoms ( LUTS) due to benign prostatic hyperplasia ( BPH) treated with either the α-blocker tamsulosin or the dual 5-alpha reductase inhibitor dutasteride, alone or in combination, as part of the 4-year Combination of Avodart and Tamsulosin ( CombAT) study., Patients and Methods CombAT was a 4-year, multicentre, randomized, double-blind, parallel-group study in 4844 men ≥50 years of age with a clinical diagnosis of BPH by medical history and physical examination, an IPSS ≥12 points, prostate volume ( PV) ≥30 mL, total serum PSA level ≥1.5 ng/mL, and Qmax >5 mL/s and ≤15 mL/s with a minimum voided volume ≥125 mL., Eligible subjects were randomized to receive oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both., Baseline variable subgroups analysed were as follows: PV (30 to <40; 40 to <60; 60 to <80; ≥80 mL), PSA level (1.5 to <2.5; 2.5 to <4; ≥4 ng/mL), age (median: <66, ≥66 years), IPSS (median: <16, ≥16; IPSS thresholds, <20, ≥20), IPSS QoL score (question 8, Q8) (median: <4, ≥4), Qmax (median: <10.4, ≥10.4 mL/s), BPH impact index ( BII) (median: <5, ≥5) and body mass index ( BMI, median: <26.8, ≥26.8 kg/m2)., Within each baseline variable subgroup, changes in IPSS, Qmax and IPSS QoL Q8 from baseline were evaluated using a generalized linear model with effects for baseline IPSS, Qmax or IPSS QoL Q8 and treatment group at each post-baseline assessment up to and including the month 48 visit using a last observation carried forward approach. The treatment comparisons of combination therapy vs dutasteride and combination therapy vs tamsulosin were performed from the general linear model with statistical significance defined as P ≤ 0.01., Results Combination therapy resulted in a significantly greater improvement from baseline IPSS at 48 months vs tamsulosin monotherapy across all baseline subgroups. The benefit of combination therapy over dutasteride was confined to groups with lower baseline PV (<60 mL) and PSA (<4 ng/mL). In groups with baseline PV ≥60 mL and PSA ≥4 ng/mL, dutasteride and combination therapy show similar improvements in symptoms., Combination therapy resulted in significantly improved Qmax compared with tamsulosin but not dutasteride monotherapy. Qmax improvement appeared to increase with PV and PSA level in combination therapy subjects., The proportion of subjects with an IPSS QoL ≤2 (at least mostly satisfied) at 48 months was significantly higher with combination therapy than with dutasteride for subgroups with PV 40-60 mL and PSA level <4 ng/mL and than with tamsulosin for all PSA subgroups and PV subgroups ≥40 mL., Conclusions Comb AT data support the use of long-term combination therapy with dutasteride and tamsulosin in patients considered at risk for progression of BPH, as determined by high PV (≥30 mL) and high PSA (≥1.5 ng/mL)., Combination therapy, dutasteride monotherapy and tamsulosin monotherapy all improved Qmax, but to different extents (combination therapy > dutasteride >> tamsulosin), suggesting that dutasteride contributes most to the Qmax benefit in combination therapy., Combination therapy provided consistent improvement over tamsulosin in LUTS across all analysed baseline variables at 48 months. Compared with dutasteride, the superiority of combination therapy at 48 months was shown in patients with PV <60 mL or PSA <4 ng/mL. [ABSTRACT FROM AUTHOR]

Aims We prospectively investigated the effect of dutasteride on clinical and urodynamic parameters in patients with benign prostatic enlargement (BPE). Materials and Methods A prospective study was conducted in consecutive 52 patients with BPE who had not been satisfied with alpha-adrenergic antagonist monotherapy. Inclusion criteria were prostate volume (PV) ≥30 ml and the International Prostate Symptom Score (IPSS) ≥8 or QOL index ≥3 under administration of an alpha-adrenergic antagonist without anticholinergic agent. Before and 24 weeks after dutasteride (0.5 mg daily) add-on treatment with preceding alpha-adrenergic antagonist, we assessed IPSS, uroflowmetry (UFM), filling cystometry, and pressure-flow study (PFS). Results Dutasteride add-on treatment significantly improved IPSS (from 18.4 ± 7.5 to 13.8 ± 7.3) and maximum flow rate (from 11.4 ± 5.6 to 13.0 ± 6.8 ml/sec). Maximum cystometric capacity on filling cystometry did not change significantly by dutasteride add-on treatment (221 ± 97 and 240 ± 104 ml before and after dutasteride add-on, respectively). All of the 41 patients with detrusor overactivity (DO) before dutasteride add-on treatment showed apparent reduction in the amplitude of involuntary detrusor contraction after dutasteride add-on treatment, including seven in whom DO disappeared. Dutasteride significantly reduced PV from 66.4 ± 31.9 to 47.6 ± 26.1 ml. In PFS, detrusor pressure at maximum flow rate (PdetQmax) significantly decreased from 71.5 ± 30.1 to 59.1 ± 24.9 cmH2O after dutasteride add-on treatment. Bladder outlet obstruction index (BOOI) also decreased significantly from 55.2 ± 31.9 to 42.3 ± 27.9, and obstruction grade assessed by the Schäfer nomogram significantly improved. Conclusions Dutasteride can improve lower urinary tract symptoms by improving storage bladder function and relieving obstruction. Neurourol. Urodynam. 32:1123-1127, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

What is known and objectives A recently published large, long-term randomized controlled trial ( RCT) brought into question the safety of dutasteride after a significantly increased risk of 'cardiac failure' was noted in the dutasteride arm of the trial compared with placebo. Our objective was to perform a meta-analysis to assess the risk of cardiovascular adverse events with the use of dutasteride for the prevention or treatment of prostatic disease. Methods We searched MEDLINE and EMBASE, unpublished articles identified through FDA/ EMEA websites, study registers of pharmaceutical companies and reference lists of articles. Parallel-group, randomized controlled trials where men received dutasteride for the prevention of prostate cancer or treatment of prostatic hyperplasia against any comparator intervention were included. Heart failure was the primary outcome of interest but we also looked at myocardial infarction and stroke. Fixed-effect meta-analysis of pooled relative risk (RR) ratios of adverse effect outcomes was conducted. Results and discussion In all, 12 RCTs were included in the meta-analysis after detailed screening of 564 citations. The total number of participants was 18 802, and study duration ranged from 6 to 208 weeks. Only two trials provided details on adequate allocation concealment, whereas all the trials stated they were double blind in nature. Dutasteride was not associated with a statistically significant increased risk of heart failure (RR 1·05; 95% confidence interval [ CI], 0·71-1·57, I2 = 20%), myocardial infarction ( RR 1·00; 95% CI 0·77-1·30, I2 = 0%) and stroke ( RR, 1·20; 95% CI 0·88-1·64, I2 = 0%) as compared to controls. What is new and conclusion We did not find consistent evidence of a significant association between dutasteride therapy and the risk of cardiovascular adverse events. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? UK clinical guidelines for treating male patients with moderate to severe LUTS associated with BPH recommend treatment with an alpha-blocker (such as tamsulosin) in cases where conservative management options have not been successful or are not appropriate. An alpha-blocker plus 5-alpha-reductase inhibitor (such as dutasteride) is recommended for those patients with moderate to severe symptoms and prostate volume >30 mL., The present study evaluates the cost-effectiveness of a new, single-dose combination of tamsulosin and dutasteride ( Combodart®) from the perspective of the UK National Health Service. The results show that the combination therapy has a high probability of being cost-effective compared with either monotherapy, and compared with the two therapies taken separately. The probability of the combination therapy being cost-effective at an incremental cost-effectiveness ratio threshold in the range £25 000-£30 000 per quality-adjusted life year is 78-88%., Objective To estimate the long-term cost-effectiveness of single-dose dutasteride/tamsulosin combination therapy as a first-line treatment for benign prostatic hyperplasia ( BPH) from the perspective of the UK National Health Service ( NHS)., Methods A Markov state transition model was developed to estimate healthcare costs and patient outcomes, measured by quality-adjusted life years ( QALYs), for patients aged ≥50 years with diagnosed BPH and moderate to severe symptoms., Costs and outcomes were estimated for two treatment comparators: oral, daily, single-dose combination therapy (dutasteride 0.5 mg + tamsulosin 0.4 mg), and oral daily tamsulosin (0.4 mg) over a period up to 25 years., The efficacy of comparators was taken from results of the Combination of Avodart and Tamsulosin ( CombAT) trial., Results Cumulative discounted costs per patient were higher with combination therapy than with tamsulosin, but QALYs were also higher., After 25 years, the incremental cost-effectiveness ratio for combination therapy was £12 219, well within the threshold range (£20 000-£30 000 per QALY) typically applied in the NHS., Probabilistic sensitivity analysis showed that the probability of combination therapy being cost-effective given the threshold range is between 78% and 88%., Conclusion Single-dose combination dutasteride/tamsulosin therapy has a high probability of being cost-effective in comparison to tamsulosin monotherapy in the UK's NHS. [ABSTRACT FROM AUTHOR]

Objective: We investigated the effects of dutasteride on urination and quality of life (QOL) in patients diagnosed with benign prostatic hyperplasia (BPH) who showed poor improvement in lower urinary tract symptoms (LUTS) with alpha-1 blockers. Methods: We retrospectively analyzed 108 patients with BPH who took dutasteride for more than 3 months from October 2009 to October 2011. The patients showed poor improvement in LUTS despite administration of alpha-1 blockers for more than 3 months; all had an International Prostate Symptom Score (IPSS) of eight or greater. We investigated changes in prostate-specific antigen and prostate volume and performed uroflowmetry and medical interviews to assess IPSS-QOL score and BPH impact index (BII). Results: Mean prostate volume was 52.8 ± 22.2 mL, and the mean period of dutasteride administration was 284 ± 118 days. Prostate volume decreased 24.1% from baseline to 6 months after administration. Voiding symptoms and storage symptoms showed improvements with longer administration periods, but only nocturia showed no clear improvement. There was a 0.9-point decrease in BII after 6 months. There was no statistically significant association between the rate of prostate volume reduction and improvement in voiding and storage symptoms. Conclusion: Additional administration of dutasteride to patients with alpha-1 blocker-resistant BPH led to improvements in all voiding and storage symptoms except nocturia, and showed no correlation between the prostate volume reduction rates and improvement in LUTS. [ABSTRACT FROM AUTHOR]

ABSTRACT An accurate and precise method was developed and validated using LC-MS/MS to quantify dutasteride in human plasma. The analyte and dutasteride-13C6 as internal standard (IS) were extracted from 300 μL plasma volume using methyl tert-butyl ether- n-hexane (80:20, v/v). Chromatographic analysis was performed on a Gemini C18 (150 × 4.6 mm, 5 µm) column using acetonitrile-5 m m ammonium formate, pH adjusted to 4.0 with formic acid (85:15, v/v) as the mobile phase. Tandem mass spectrometry in positive ionization mode was used to quantify dutasteride by multiple reaction monitoring. The entire data processing was done using Watson LIMSTM software, which provided excellent data integrity and high throughput with improved operational efficiency. The calibration curve was linear in the range of 0.1-25 ng/mL, with intra-and inter-batch values for accuracy and precision (coefficient of variation) ranging from 95.8 to 104.0 and from 0.7 to 5.3%, respectively. The mean overall recovery across quality controls was ≥95% for the analyte and IS, while the interference of matrix expressed as IS-normalized matrix factors ranged from 1.01 to 1.02. The method was successfully applied to support a bioequivalence study of 0.5 mg dutasteride capsules in 24 healthy subjects. Assay reproducibility was demonstrated by reanalysis of 103 incurred samples. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND. Two recent chemoprevention trials demonstrated significant reductions in overall prostate cancer incidence. However, a possible increase in high-grade disease has raised concerns that the harms of the drugs, including mortality because of high-grade disease, may outweigh the benefits. The authors attempted to estimate the effect of these drugs on prostate cancer mortality to be able to better evaluate the cost-benefit tradeoff. METHODS. The authors analyzed prostate cancer incidence in the Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which evaluated finasteride and the related compound dutasteride, respectively (both vs placebo). They used 13-year prostate cancer survival data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial to project prostate cancer mortality from incidence patterns; survival rates were applied to incident cancers according to prognostic strata, which were defined by Gleason score, prostate-specific antigen level, and clinical stage. For PCPT, the analysis was performed using both original trial results and previously published adjusted analyses that attempted to account for artifacts related to the drugs' effect on prostate volume. RESULTS. For the PCPT trial, the estimated relative risk (RR) for prostate cancer mortality was 1.02 (95% confidence interval [95% CI], 0.85-1.23) using the original trial results and 0.87 (95% CI, 0.72-1.06) and 0.91 (95% CI, 0.76-1.09) based on the adjusted PCPT analyses. For the REDUCE trial, the RR for prostate cancer mortality was 0.93 (95% CI, 0.80-1.08). CONCLUSIONS. Projecting a mortality outcome of the PCPT and REDUCE trials as an approach to weighing benefits versus harms suggests at most a small increase in prostate cancer mortality in the treatment arms, and possibly a modest decrease. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The second to fourth digit ratio (hereafter the digit ratio) of the right hand is related to the activity of the androgen receptor. Five α-reductase inhibitor (5ARI) reduces the prostate volume of patients with BPH. In terms of prostate volume reduction, large-scale placebo-controlled studies show that patients with BPH do not always respond well to 5ARI treatment. Patients with a higher digit ratio respond well to dutasteride treatment compared to those with a lower digit ratio. These results suggest that the digit ratio might be a predictor of the response to dutasteride treatment. OBJECTIVE To investigate the relationship between second to fourth digit ratio (hereafter the digit ratio) and prostate volume reduction by dutasteride treatment., PATIENTS AND METHODS A total of 142 men aged ≥40 years with a clinical diagnosis of benign prostatic hyperplasia and an enlarged prostate (prostate volume ≥30 mL) were prospectively enrolled., Before prostate-specific antigen (PSA) level determination and transrectal ultrasonography (TRUS), the lengths of the second and fourth digits of the right hand were measured by an investigator using a digital vernier calliper., Using TRUS, pre- and post-treatment prostate volume (PV1 and PV2) were measured by an uroradiologist who was unaware of finger lengths. We investigated the change in prostate volume and PSA level at least 6 months after the initiation of dutasteride therapy., RESULTS When the patients were divided into two groups according to digit ratio (A: digit ratio <0.95, n= 71; B: digit ratio ≥0.95, n= 71), there was a greater reduction in prostate volume in group B compared to group A (PV2-PV1: −9.4 mL vs −13.2 mL, P= 0.042; [PV2-PV1]/PV1: −17.5% vs −24.5%, P= 0.027; [PV2-PV1]/duration: −1.1 mL/month vs −1.6 mL/month, P= 0.041; [PV2-PV1]/PV1/duration: −2.0%/month vs −3.0%/month, P= 0.016)., Significant negative correlations were found between the digit ratio and reduction rate ([PV2-PV1]/duration: r=−0.165, P= 0.049; [PV2-PV1]/PV1/duration: r=−0.191, P= 0.023)., CONCLUSIONS Patients with higher digit ratios respond well to dutasteride treatment., The results obtained in the present study suggest that the digit ratio is a predictor of the response to dutasteride treatment. [ABSTRACT FROM AUTHOR]

The Combination of Avodart and Tamsulosin study was a 4-year, randomized, double-blind study of the efficacy and safety of dutasteride and tamsulosin, alone or in combination, in men with moderate-to-severe benign prostatic hyperplasia. In this post-hoc investigation, we analyzed primary and secondary end-points from the Combination of Avodart and Tamsulosin study in Asian ( n = 325) and Caucasian men ( n = 4259). The incidence of acute urinary retention or benign prostatic hyperplasia-related surgery did not differ significantly between treatment groups in the Asian subpopulation. In Caucasian men, the incidence of acute urinary retention/benign prostatic hyperplasia-related surgery was significantly lower in the combination therapy group compared with the tamsulosin monotherapy group ( P < 0.001), but not compared with dutasteride monotherapy. Combination therapy significantly increased the time to benign prostatic hyperplasia clinical progression and resulted in improved International Prostate Symptom Score, maximum urinary flow rate, quality of life, and reduced prostate volume in Asian and Caucasian men who received combination therapy compared with tamsulosin monotherapy. Combination therapy also significantly improved ( P < 0.05) time to benign prostatic hyperplasia clinical progression, International Prostate Symptom Score, maximum urinary flow rate and quality of life versus dutasteride in the Caucasian subpopulation. The adverse-event profile was comparable between subpopulations. In conclusion, Asian and Caucasian men respond similarly to these treatments, despite apparent racial differences in 5α-reductase activity. [ABSTRACT FROM AUTHOR]

OBJECTIVE • To assess the efficacy and safety of dutasteride compared with finasteride in treating men with symptomatic benign prostatic hyperplasia (BPH) for 12 months. PATIENTS AND METHODS • The Enlarged Prostate International Comparator Study was a multicentre, randomized, double-blind, 12-month, parallel-group study. • Men aged ≥ 50 years with a clinical diagnosis of BPH received once-daily treatment with dutasteride 0.5 mg ( n = 813) or finasteride 5 mg ( n = 817). After a 4-week placebo run-in period, patients were randomized to receive dutasteride or finasteride for 48 weeks, followed by an optional 24-month, open-label phase, during which patients received dutasteride 0.5 mg once daily. • The primary endpoint was change in prostate volume, and the secondary endpoints included improvement in American Urological Association Symptom Index (AUA-SI) scores, improvement in maximum urinary flow rate (Qmax ) and longterm safety in the 24-month open-label phase. RESULTS • Both dutasteride and finasteride were effective at reducing prostate volume with no significant difference between the two treatments during the study. • Similar reductions in mean AUA-SI scores and Qmax were also observed for men in both treatment groups. • A similar percentage of adverse events was experienced by patients of both treatment groups, and no new adverse events were reported in the open-label phase. CONCLUSION • Dutasteride and finasteride, when administered for 12 months, were similarly effective in reducing prostate volume and improving Qmax and urinary symptoms associated with BPH in men with an enlarged prostate. [ABSTRACT FROM AUTHOR]

OBJECTIVE • To identify predictors of sexual dysfunction using baseline data from the reduction by dutasteride of prostate cancer events (REDUCE) study. PATIENTS AND METHODS • REDUCE was a 4-year randomized, double-blind, placebo-controlled studyevaluating the efficacy and safety of once-daily dutasteride 0.5 mg in over 8000 men aged 50–75 years with a prostate-specific antigen (PSA) level of 2.5–10 ng/mL (50–60 years) or 3.0–10 ng/mL ( > 60 years) and a negative prostate biopsy within 6 months of enrolment. • Baseline values (mean serum testosterone, age, International Prostate Symptom Score [IPSS], total prostate volume [TPV], body mass index [BMI], and presence of diabetes/ glucose intolerance) were compared in subjects with and without sexual dysfunction (sexual inactivity, impotence, decreased libido or a Problem Assessment Scale of the Sexual Function Index [PAS-SFI] score < 9). RESULTS• Multivariate logistic regression showed that baseline age and IPSS were significant predictors of all four sexual function criteria examined ( P< 0.0001). • BMI was a significant predictor of decreased libido, impotence and a PAS-SFI score < 9, while diabetes/glucose intolerancewas a significant predictor of sexual inactivity, impotence and a PAS-SFI score < 9. • Testosterone and TPV were not significant predictors of any sexual function criterionexamined. CONCLUSIONS • Age, IPSS, BMI and diabetes/glucose intolerance, but not serum testosterone or TPV, were significant independentpredictors of sexual dysfunction in the REDUCE study population. • The lack of association between sexual dysfunction and serum testosterone questions the value of modestly reduced or low normal testosterone levels as criteria for choosing testosterone replacement in older men with sexual dysfunction. [ABSTRACT FROM AUTHOR]

OBJECTIVE: • To assess the effects of combined therapy with dutasteride and tamsulosin on voiding and storage symptoms compared with those of dutasteride or tamsulosin alone, using 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study. PATIENTS AND METHODS:• Men ( n = 4844) aged ≥ 50 years with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH), a prostate volume of ≥ 30 mL, and a serum prostate-specific antigen level of 1.5–10 ng/mL. • CombAT was a multicentre, double-blind, parallel-group study. • Oral dutasteride (0.5 mg) or tamsulosin (0.4 mg) alone or in combination was taken daily for 4 years. • Mean changes from baseline in storage and voiding symptoms at 4 years were assessed using subscales of the International Prostate Symptom Score. RESULTS: • At 4 years, the mean reduction in the storage subscore was significantly greater in the combined therapy group vs the dutasteride (adjusted mean difference − 0.43) and tamsulosin (adjusted mean difference − 0.96) monotherapy groups ( P < 0.001). • Also at 4 years, the mean reduction in the voiding subscore was significantly greater in the combined therapy group vs the dutasteride (adjusted mean difference − 0.51) and tamsulosin (adjusted mean difference − 1.60) monotherapy groups ( P < 0.001). • The improvement in the storage subscore with combined therapy was significantly better ( P < 0.001) than dutasteride and tamsulosin from 3 months and 12 months, respectively. Similarly, the improvement in the voiding subscore with combined therapy was significantly better than dutasteride ( P < 0.001) and tamsulosin ( P ≤ 0.006) from 3 months and 6 months, respectively. • Improvements in the storage and voiding symptom subscores with combined therapy were achieved irrespective of prostate volume, although in men with the highest baseline prostate volumes ( ≥ 58 mL), combined therapy was not better than dutasteride. CONCLUSIONS: • In men with a prostate volume of ≥ 30 mL, combined therapy with dutasteride plus tamsulosin provided better long-term (up to 4 years) control of both storage and voiding LUTS compared with tamsulosin monotherapy. • Combined therapy was better than dutasteride monotherapy in men with prostate volumes of ≥ 30 to < 58 mL, but not in men with a prostate volume of ≥ 58 mL. [ABSTRACT FROM AUTHOR]